Evidence map›Paper›PMID 27998643›Full record

ArticleKidney international2017

Activated ERK1/2 increases CD44 in glomerular parietal epithelial cells leading to matrix expansion.

Sebastian S Roeder, Taylor J Barnes, Jonathan S Lee, India Kato, Diana G Eng, Natalya V Kaverina, Maria W Sunseri, Christoph Daniel, Kerstin Amann, Jeffrey W Pippin and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Kidney international, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.6field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 65 citations in OpenAlex.

  1. Article
  2. Article
  3. Injury-induced paracrine effects on the podocyte's transcriptome.American journal of physiology. Renal physiology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Sebastian S RoederDivision of Nephrology, University of Washington, Seattle, Washington, USA; Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Taylor J BarnesDivision of Nephrology, University of Washington, Seattle, Washington, USA; Department of Biology, Oregon State University, Corvallis, Oregon, USA.
Jonathan S LeeDivision of Nephrology, University of Washington, Seattle, Washington, USA.
India KatoDivision of Nephrology, University of Washington, Seattle, Washington, USA.
Diana G EngDivision of Nephrology, University of Washington, Seattle, Washington, USA.
Natalya V KaverinaDivision of Nephrology, University of Washington, Seattle, Washington, USA.
Maria W SunseriDivision of Nephrology, University of Washington, Seattle, Washington, USA.
Christoph DanielDepartment of Nephropathology, University of Erlangen-Nürnberg, Erlangen, Germany.
Kerstin AmannDepartment of Nephropathology, University of Erlangen-Nürnberg, Erlangen, Germany.
Jeffrey W PippinDivision of Nephrology, University of Washington, Seattle, Washington, USA.
Stuart J ShanklandDivision of Nephrology, University of Washington, Seattle, Washington, USA. Electronic address: stuartjs@uw.edu.
University of Washington · USFriedrich-Alexander-Universität Erlangen-Nürnberg · DE

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Karin E Bornfeldt · 1986 to 2026
$41.4M
Juxta-glomerular cells serve as glomerular epithelial cell progenitors in glomerular diseaseR01DK097598 · NIDDK · UNIVERSITY OF WASHINGTON · PI SHANKLAND, STUART JAMES, WESSELY, OLIVER · 2014 to 2022
$5.2M
CELL CYCLE PROTEINS AND GLOMERULAR APOPTOSISR01DK056799 · NIDDK · UNIVERSITY OF WASHINGTON · PI SHANKLAND, STUART JAMES · 2000 to 2014
$3.6M
NIDDK NIH HHS P30 DK017047NIDDK NIH HHS R01 DK056799NIDDK NIH HHS R01 DK097598
6 · The paper itself

Abstract

The glycoprotein CD44 is barely detected in normal mouse and human glomeruli, but is increased in glomerular parietal epithelial cells following podocyte injury in focal segmental glomerulosclerosis (FSGS). To determine the biological role and regulation of CD44 in these cells, we employed an in vivo and in vitro approach. Experimental FSGS was induced in CD44 knockout and wild-type mice with a cytotoxic podocyte antibody. Albuminuria, focal and global glomerulosclerosis (periodic acid-Schiff stain), and collagen IV staining were lower in CD44 knockout compared with wild-type mice with FSGS. Parietal epithelial cells had lower migration from Bowman's capsule to the glomerular tuft in CD44 knockout mice with disease compared with wild type mice. In cultured murine parietal epithelial cells, overexpressing CD44 with a retroviral vector encoding CD44 was accompanied by significantly increased collagen IV expression and parietal epithelial cell migration. Because our results showed de novo co-staining for activated ERK1/2 (pERK) in parietal epithelial cells in experimental FSGS, and also in biopsies from patients with FSGS, two in vitro strategies were employed to prove that pERK regulated CD44 levels. First, mouse parietal epithelial cells were infected with a retroviral vector for the upstream kinase MEK-DD to increase pERK, which was accompanied by increased CD44 levels. Second, in CD44-overexpressing parietal epithelial cells, decreasing pERK with U0126 was accompanied by reduced CD44. Finally, parietal epithelial cell migration was higher in cells with increased and reduced in cells with decreased pERK. Thus, pERK is a regulator of CD44 expression, and increased CD44 expression leads to a pro-sclerotic and migratory parietal epithelial cell phenotype.

Indexed as

AlbuminuriaAnimalsCell MovementCells, CulturedCollagen Type IVDisease Models, AnimalEnzyme ActivationExtracellular MatrixGenetic Predisposition to DiseaseGlomerulosclerosis, Focal SegmentalHumansHyaluronan ReceptorsKidney GlomerulusMaleMice, KnockoutMitogen-Activated Protein Kinase 1CD44 protein, humanCd44 protein, mouseCollagen Type IVHyaluronan ReceptorsMapk1 protein, mouseMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Protein Kinase InhibitorscollagenFSGSglomerulosclerosisglomerulusmitogen-activated protein kinasespodocyte

Identifiers

PMID27998643
PMCPMC5357449
OpenAlexW2562401512

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.